Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress. Marked reduction in CRH has been observed in association with Alzheimer's disease, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially-fatal metabolic consequences including hypoglycemia and hepatitis. In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta. In the placenta, CRH is a marker that determines the length of gestation and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, CRH may act as a trigger for parturition.[1]

The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of Generalized anxiety disorder in women.[3] Another CRH-1 antagonist antalarmin has been researched in animal studies for the treatment of anxiety, depression and other conditions, but no human trials with this compound have been carried out.

Levels rise towards birth and current theory suggests three roles of CRH in parturition:[8]

Increases level so dehydroepiandrosterone (DHEA) directly by action on the fetal adrenal gland, and indirectly via the mother's pituitary gland. DHEA has a role in preparing for and stimulating cervical contractions.

Prior to parturition it may have a role inhibiting contractions, through increasing cAMP levels in the myometrium.

In culture, trophoblast CRH is inhibited by progesterone, which remains high throughout pregnancy. Its release is stimultated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.[9]

Heim, C., Owens, M. J., Plotsky, P. M., & Nemeroff, C. B. (1997). The role of early adverse life events in the etiology of depression and posttraumatic stress disorder. Focus on corticotropin-releasing factor. New York, NY: New York Academy of Sciences.

Jochman, K. A. (2004). The functional role of the corticotropin-releasing factor (CRF) system in the amygdala: Molecular, behavioral, and anatomical studies. Dissertation Abstracts International: Section B: The Sciences and Engineering.

Lee, Y., & Davis, M. (1997). Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex: Journal of Neuroscience Vol 17(16) Aug 1997, 6434-6446.

Lee, Y., & Davis, M. (1997). Role of the septum in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex: Journal of Neuroscience Vol 17(16) Aug 1997, 6424-6433.

Moreau, J.-L., Kilpatrick, G., & Jenck, F. (1997). Urocortin, a novel neuropeptide with anxiogenic-like properties: Neuroreport: An International Journal for the Rapid Communication of Research in Neuroscience Vol 8(7) May 1997, 1697-1701.

Morris, J. F. (2001). How does the brain determine whether enhanced cognition or anxiety is the appropriate response to a stress? : Neuroreport: For Rapid Communication of Neuroscience Research Vol 12(6) May 2001, A35.

Nemeroff, C. B. (1999). The preeminent role of neuropeptide systems in the early pathophysiology of Alzheimer disease: Up with corticotropin-releasing factor, down with acetycholine: Archives of General Psychiatry Vol 56(11) Nov 1999, 991-992.